A wide variety of reagents such as Na cyanate, acid anhydride, sulfonyl chloride and lactone derivatives, which irreversibly bind amino groups, have been shown to inhibit rosette formation between human lymphocytes and sheep erythrocytes (E-rosettes), an in vitro reaction characteristic of thymus-dependent lymphocytes (T cells). In addition, Na cyanate used in vivo appears to suppress T cell-dependent and not T cell-independent lymphocyte functions in inbred mice. It is the purpose of this investigation to explore the mechanism by which the amino group-binding reagents exert these effects, and to apply the information acquired to the development of new methods of immunoregulation, primarily as it applies to cell-mediated immunity. The study will be performed on human blood lymphocytes and in experimental animals in several phases. Initially, optimal methods will be developed for the in vitro treatment of lymphocytes, and for the in vivo administration of these compounds according to schedules which minimize their toxicity. Effects of the in vitro treatment will be evaluated on such in vitro lymphocyte functions as E-rosette formation and response to various mitogens and allogeneic cells in tissue culture media. Lymphocytes, treated in vitro, will also be studied for their in vivo behavior and functions such as survival, homing-in, and various types of immune responses including graft-versus-host reactivity. These functions will be evaluated in T cell-deprived (B cell) mice. Should the in vitro treatment result in production of nonviable cells, then in vivo treated cells will be harvested from animals who have received the drugs for several days in advance. Transfer of these cells into B cell mice would provide a means by which the capability of the treated cells to perform their immunological functions can be evaluated. The amino group-binding reagents will also be administered first to mice, and subsequently to other experimental animals, with the purpose of selectively modifying their response to transplanted normal tissue, to transplanted malignant cells, and to their own tissues as in natural or experimentally-induced autoimmune diseases. This study would have major implications in the understanding of cell communication and T cell receptors, and may result in the development of new methods for regulation of cell-mediated immunity in man.